The present invention relates to system and methods for generating a profile of particulate components of a body fluid sample. More particularly, embodiments of the present invention relate to a system and method which can be utilized to detect and diagnose an inflammatory condition in an individual.
Diagnosis of various clinical conditions is many times based on the determination of the presence and/or level of several components present in body fluids, mainly in the blood. Such body fluid evaluation provides information about the physiological and clinical state of an individual and can be indicative of the presence, absence and at times progression of an illness.
A widely accepted medical school doctrine teaches that the complete blood count including the white blood cell differential (CBC+Diff) is one of the best tests for assessing a patient's overall health. With it, a physician can detect or diagnose for example, anemia, infection, blood loss, acute and chronic diseases, allergies, and other conditions characterized by deviation from normal values and thus to identify the existence and assess the severity of the patient's condition in order to propose a future therapeutic approach. Moreover, CBC+Diff analysis provide comprehensive information on blood constituents, including the number of red blood cells, hematocrit, hemoglobin concentration, and on indices that portray the size, shape, and oxygen-carrying characteristics of the entire red blood cell (RBC) population. The CBC+Diff also includes the number and types of white blood cells and the number of platelets. Thus, CBC+Diff is one of the most frequently requested diagnostic tests with about two billion done in the United States per year.
One of the most common phenomena which accompany many disorders and diseases is the inflammatory response. Inflammation results from a complex of cellular and humoral events which arise as a response to many stimuli such as impact, distortion, chemical irritation, infection by pathogenic organisms (such as bacteria or viruses) or extreme temperatures. The development of an inflammatory response is accompanied by an acute phase response in which various kinds of proteins such as, for example, fibrinogen, haptoglobin, ceruloplasmin, ferritin and c-reactive proteins are synthesized. Typically, the most common parameters which are tested in order to diagnose inflammation in an individual are the total white blood cell (leukocytes) count (WBCC), red blood cell (erythrocytes) sedimentation rate (ESR) and quantitative C-reactive protein (CRP) which allow the discrimination between the presence or the absence of an inflammatory response.
Tests which are used to determine parameters associated with inflammation are typically carried out automatically by instruments such as automated counters, laser nephelometers or automatic ELISA readers, which are capable of counting and classifying different components of the body fluid sample on the basis of predefined characteristics (such as size, shape and concentration).
A main problem in such automated systems stems from the fact that the components of body fluid and in particular the cellular components are in fact dynamic components which interact with one another and thus their physical characteristics may not fall within the exact predefined characteristics of the automated instrument. Thus for example, many of the proteins synthesized during the acute phase response of an inflammation, cause the cells to aggregate with cells of the same type as well as with cells of other types. An aggregate comprised of several cells may be classified by the automated device as a large unclassified cell (LUC) while, in fact each of the cells comprising the aggregate should have been added to the specific cell population count to which they belong. The result of such an error in classification can, for instance, bring about an erroneous WBCC and thus to an erroneous diagnosis of pseudoleukopenia. In addition, it is also common that a WBCC result which is within normal limits is obtained by routinely used methods (mainly by electronic counters) while, in actuality, the WBCC is substantively higher. Such an erroneous “normal” WBCC may substantively influence the diagnostic decision of a physician and result in non-effective or even harmful treatment.
Furthermore, currently utilized methods for evaluating body fluids which utilize automated instruments require relatively large amounts of body fluid such as a blood sample in order to perform the evaluation. This may be problematic in cases where large volumes of the body fluid are not available for diagnosis, such as the case in newborns. This problem becomes even more severe in view of the fact that, in most cases, in order for a physician to diagnose a certain condition in an individual, it is necessary to carry out at least two separate tests, each requiring a separate sample. Typically, one test will be a total white blood cell count and often also a differential count in which white blood cells of each subpopulation (e.g. neutrophils, lymphocytes, etc.) are counted separately. The other test will typically be an erythrocyte sedimentation rate (ESR) test.
An additional drawback to presently used methods arises from the fact that due to the relatively large amounts of body fluids required for each diagnostic test, it is difficult to repeat the diagnostic test over short intervals of time. This drawback imposes severe limitations on diagnosis using such methods since test repetition is often required for monitoring the progression of a clinical condition over time.
It is known that white blood cells change their adherence properties and aggregation tendencies during inflammation since their membranes become more “sticky”. A leukocyte adhesiveness/aggregation test (LAAT) based on the aggregation of cells in a body fluid to one another, was described previously as a tool for diagnosing the presence of an inflammatory response and assessment of its severity in various disorders and diseases. LAAT has also been proposed as a method of discriminating between bacterial infections (in which there is a high level of leukocyte aggregation) and viral infections (wherein attenuated or no leukocyte aggregation is detected). Aggregation of other types of cells such as erythrocytes and platelets has also been correlated to various conditions involving inflammation but these parameters have not been used for diagnosis of such conditions.
Another limitation inherent to presently utilized diagnostic systems arises from the fact that due to the complexity of tests and equipment involved, the use of such systems in telemedicine cannot be easily effected.
Telemedicine is the process of sending test data and/or images from one point to another through networks, typically over standard telephone lines, or over a wide-area network using dial-up ISDN lines or other switched digital services. Using telemedicine, images can be sent from one part of a hospital to another part of the same hospital, from one hospital to another, from remote sites to diagnostic centers, etc. In other words, test data and/or images obtained at one location can be sent to almost any place in the world.
As cost-effective diagnosis becomes a major issue, telemedicine is becoming an acceptable way to make diagnoses and to consult with referring physicians. Computer-assisted transfer of digitized images allows geographically dispersed consultants to lend their expertise to remote regions, thereby benefiting patients who now may have limited access to advanced medical services. Telemedicine systems are especially important in rural medical facilities, where skilled physicians or automated analysis systems are not available.
There is thus a widely recognized need for, and it would be highly advantageous to have, a system and method which can be utilized to manually or automatically analyze biological samples such as blood samples to thereby enable diagnosis of patient's clinical condition, while being easily implementable and utilizable in telemedical architecture.